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A Dynamic Mode of Mitotic Bookmarking by Transcription Factors

Sheila S. Teves, Luye An, Anders S. Hansen, Liangqi Xie, Xavier Darzacq, Robert Tjian
doi: https://doi.org/10.1101/066464
Sheila S. Teves
1Department of Molecular and Cell Biology, Li Ka Shing Center for Biomedical and Health Sciences, CIRM Center of Excellence, University of California, Berkeley, CA 94720, USA
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Luye An
1Department of Molecular and Cell Biology, Li Ka Shing Center for Biomedical and Health Sciences, CIRM Center of Excellence, University of California, Berkeley, CA 94720, USA
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Anders S. Hansen
1Department of Molecular and Cell Biology, Li Ka Shing Center for Biomedical and Health Sciences, CIRM Center of Excellence, University of California, Berkeley, CA 94720, USA
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Liangqi Xie
1Department of Molecular and Cell Biology, Li Ka Shing Center for Biomedical and Health Sciences, CIRM Center of Excellence, University of California, Berkeley, CA 94720, USA
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Xavier Darzacq
1Department of Molecular and Cell Biology, Li Ka Shing Center for Biomedical and Health Sciences, CIRM Center of Excellence, University of California, Berkeley, CA 94720, USA
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  • For correspondence: jmlim@berkeley.edu darzacq@berkeley.edu
Robert Tjian
1Department of Molecular and Cell Biology, Li Ka Shing Center for Biomedical and Health Sciences, CIRM Center of Excellence, University of California, Berkeley, CA 94720, USA
2Howard Hughes Medical Institute, Berkeley, CA 94720, USA
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  • For correspondence: jmlim@berkeley.edu darzacq@berkeley.edu
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Summary

During mitosis, transcription is shut off, chromatin condenses, and most transcription factors (TFs) are reported to be excluded from chromosomes. How do daughter cells re-establish the original transcription program? Recent discoveries that a select set of TFs remain bound on mitotic chromosomes suggest a potential mechanism for maintaining transcriptional programs through the cell cycle termed mitotic bookmarking. Here we report instead that many TFs remain associated with chromosomes, and that the exclusion previously described is largely a fixation artifact. In particular, most TFs we tested are significantly enriched on mitotic chromosomes. Studies with Sox2 reveal that this mitotic interaction is more dynamic than in interphase and requires both DNA binding and nuclear import. Furthermore, this dynamic mode results from lack of transcriptional activation rather than decreased accessibility of underlying DNA sequences in mitosis. The nature of the cross-linking artifact prompts careful re-examination of the role of TFs in mitotic bookmarking.

Highlights

  • Many transcription factors bind to mitotic chromosomes

  • Sox2 mitotic interaction is dynamic and requires DNA binding and nuclear import

  • DNA remains highly accessible in mitotic chromosomes

  • Formaldehyde-based cross-linking leads to mis-localization of TFs

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted August 01, 2016.
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A Dynamic Mode of Mitotic Bookmarking by Transcription Factors
Sheila S. Teves, Luye An, Anders S. Hansen, Liangqi Xie, Xavier Darzacq, Robert Tjian
bioRxiv 066464; doi: https://doi.org/10.1101/066464
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A Dynamic Mode of Mitotic Bookmarking by Transcription Factors
Sheila S. Teves, Luye An, Anders S. Hansen, Liangqi Xie, Xavier Darzacq, Robert Tjian
bioRxiv 066464; doi: https://doi.org/10.1101/066464

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